TGF beta-mediated signaling and transcriptional regulation in pancreatic development and cancer

Transforming growth factor-beta (TGF beta) plays a critical role in pancrea tic development and cell proliferation. Binding of TGF beta to its membrane receptor kinases activates the Smad signaling proteins, allowing them to t ranslocate to the nucleus and participate in the transcriptional control of TGF target genes. In addition, there is an increasing number of cellular m echanisms affecting the final response of a cell to TGF beta. This includes crosstalk with other signaling pathways and the induction of TGF beta earl y response genes, such as the TGF beta -inducible early response gene (TIEG ) family of transcription factors. Like the Smads, TIEGs behave as downstre am effector proteins in TGF beta -mediated pancreatic growth control. The d iscovery of the Smads and TIEGs has provided new insights into TGF beta -re gulated functions. Their significance in pancreatic development and cancer is discussed in this review. Curr Opin Gastroenterol 2001, 17:434-440 (C) 2 001 Lippincott Williams & Wilkins, Inc.